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Journal of Virology, December 2007, p. 13681-13693, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01702-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Altered Pathogenesis of Porcine Respiratory Coronavirus in Pigs due to Immunosuppressive Effects of Dexamethasone: Implications for Corticosteroid Use in Treatment of Severe Acute Respiratory Syndrome Coronavirus{triangledown}

Kwonil Jung, Konstantin P. Alekseev, Xinsheng Zhang, Doo-Sung Cheon, Anastasia N. Vlasova, and Linda J. Saif*

Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, Ohio 44691

Received 6 August 2007/ Accepted 28 September 2007

The pathogenesis and optimal treatments for severe acute respiratory syndrome (SARS) are unclear, although corticosteroids were used to reduce lung and systemic inflammation. Because the pulmonary pathology of porcine respiratory coronavirus (PRCV) in pigs resembles SARS, we used PRCV as a model to clarify the effects of the corticosteroid dexamethasone (DEX) on coronavirus (CoV)-induced pneumonia. Conventional weaned pigs (n = 130) in one of four groups (PRCV/phosphate-buffered saline [PBS] [n = 41], PRCV/DEX [n = 41], mock/PBS [n = 23], and mock/DEX [n = 25]) were inoculated intranasally and intratracheally with the ISU-1 strain of PRCV (1 x 107 PFU) or cell culture medium. DEX was administered (once daily, 2 mg/kg of body weight/day, intramuscularly) from postinoculation day (PID) 1 to 6. In PRCV/DEX pigs, significantly milder pneumonia, fewer PRCV-positive cells, and lower viral RNA titers were present in lungs early at PID 2; however, at PID 4, 10, and 21, severe bronchointerstitial pneumonia, significantly higher numbers of PRCV-positive cells, and higher viral RNA titers were observed compared to results for PRCV/PBS pigs. Significantly lower numbers of CD2+, CD3+, CD4+, and CD8+ T cells were also observed in lungs of PRCV/DEX pigs than in those of PRCV/PBS pigs at PID 8 and 10, coincident with fewer gamma interferon (IFN-{gamma})-secreting cells in the tracheobronchial lymph nodes as determined by enzyme-linked immunospot assay. Our results confirm that DEX treatment alleviates PRCV pneumonia early (PID 2) in the infection but continued use through PID 6 exacerbates later stages of infection (PID 4, 10, and 21), possibly by decreasing cellular immune responses in the lungs (IFN-{gamma}-secreting T cells), thereby creating an environment for more-extensive viral replication. These data have potential implications for corticosteroid use with SARS-CoV patients and suggest a precaution against prolonged use based on their unproven efficacy in humans, including possible detrimental secondary effects.

* Corresponding author. Mailing address: Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, 1680 Madison Ave., Wooster, Ohio 44691. Phone: (330) 263-3744. Fax: (330) 263-3677. E-mail: saif.2{at}osu.edu

{triangledown} Published ahead of print on 17 October 2007.

Journal of Virology, December 2007, p. 13681-13693, Vol. 81, No. 24
0022-538X/07/$08.00+0     doi:10.1128/JVI.01702-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jung, K., Renukaradhya, G. J., Alekseev, K. P., Fang, Y., Tang, Y., Saif, L. J. (2009). Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections. J. Gen. Virol. 90: 2713-2723 [Abstract] [Full Text]  
  • Zhang, X., Alekseev, K., Jung, K., Vlasova, A., Hadya, N., Saif, L. J. (2008). Cytokine Responses in Porcine Respiratory Coronavirus-Infected Pigs Treated with Corticosteroids as a Model for Severe Acute Respiratory Syndrome. J. Virol. 82: 4420-4428 [Abstract] [Full Text]  


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